chr18-57545828-A-AG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000140.5(FECH):​c.*4883_*4884insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 152,252 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 15 hom., cov: 32)

Consequence

FECH
NM_000140.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.35
Variant links:
Genes affected
FECH (HGNC:3647): (ferrochelatase) The protein encoded by this gene is localized to the mitochondrion, where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Mutations in this gene are associated with erythropoietic protoporphyria. Two transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome 3.[provided by RefSeq, May 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 18-57545828-A-AG is Benign according to our data. Variant chr18-57545828-A-AG is described in ClinVar as [Likely_benign]. Clinvar id is 327329.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FECHNM_000140.5 linkuse as main transcriptc.*4883_*4884insC 3_prime_UTR_variant 11/11 ENST00000262093.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FECHENST00000262093.11 linkuse as main transcriptc.*4883_*4884insC 3_prime_UTR_variant 11/111 NM_000140.5 P22830-1
FECHENST00000652755.1 linkuse as main transcriptc.*4883_*4884insC 3_prime_UTR_variant 11/11 P22830-2

Frequencies

GnomAD3 genomes
AF:
0.00622
AC:
947
AN:
152134
Hom.:
15
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000821
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0300
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.0564
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00904
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000647
Gnomad OTH
AF:
0.00478
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00627
AC:
954
AN:
152252
Hom.:
15
Cov.:
32
AF XY:
0.00729
AC XY:
543
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000818
Gnomad4 AMR
AF:
0.0305
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.0563
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00904
Gnomad4 NFE
AF:
0.000647
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00410
Hom.:
3
Bravo
AF:
0.00948

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Protoporphyria, erythropoietic, 1 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201434287; hg19: chr18-55213060; API